Alcohol and drug abuse pose serious medical, social, and economic problems in the United States and around the world. Our objective is to establish an "Alternative Medicine Center for Alcohol and Drug Abuse" within the CERC program to enable researchers and clinicians to evaluate the efficacy of certain complementary and alternative medicine therapies and practices for the prevention of relapse and craving for alcohol and drugs, and to provide insight into the mechanisms of action. Addiction is characterized by compulsive use, tolerance, dependence, craving, and relapse. It is a complex process with physiological, behavioral, psychological, and social components, so treatment is usually multifaceted. There are two fundamental approaches: prevention of the onset of compulsive use, and prevention of relapse and the craving that leads to relapse. In the past, much medical attention has been directed at the symptoms of acute abstinence (detoxification), and these symptoms can be treated with available medications. However, relapse, which is often precipitated by withdrawal (stress and anxiety) and/or intense craving even after prolonged abstinence, poses a serious therapeutic challenge. Therefore, the central theme of this project is to evaluate the traditional Chinese herbal remedies YGT (NPI-025) and XJL (NPI-028) and a non-invasive HANS electrical acupuncture technique for prevention of relapse in animal and patients and to provide scientific support for determining mechanism of action of these alternative therapies. This program consists of four interactive Scientific Research Projects, each of which is necessary for successful completion of the whole. Project 1 will focus on the procurement, standardization, and fractionation of the two herbal remedies, and to conduct in vitro screening of Chinese herbal remedies and fractions for their affinity at the mu, delta, and kappa opioid receptors, the nociceptin/orphanin FQ (N/OFQ) receptor and D 1 and D2 dopamine receptors and for their receptor functions by [35S]GTPgammaS binding and adenylyl cyclase activity. Project 2 will evaluate the herbal remedies and fractions for prevention of alcohol/drug relapse in a sequential animal models. Project 3 will evaluate HANS method with low- and high-frequency electrical acupuncture for prevention of alcohol and drug abuse in animal and human. The sites of action in the brain induced by electrical acupuncture alone or in combination with herbal remedies will be monitored by f-MRI. In brief, acupuncture through transcutaneous electrical stimulation (HANS method) is a highly attractive alternative therapy for the treatment of drug abuse. It is a non-invasive and safe physical therapy, which allows the body to release its own natural chemicals to prevent drug relapse. Project 4 will be a clinical evaluation of the herbal remedies for prevention of alcohol/drug relapse. Administrative Core A, based at McLean Hospital (affiliated with Harvard Medical School) and assisted by an Extemal Scientific Board, will coordinate these scientific activities, provide statistical services, obtain local IRB approval, and ensure that the overall objective will be accomplished in the most effective manner.